The clinical relevance of serum versus CSF NMDAR autoantibodies associated exclusively with psychiatric features: a systematic review and meta-analysis of individual patient data

BACKGROUND: A variety of psychiatric syndromes are associated with NMDAR autoantibodies; however, their clinical relevance when only present in the serum is unclear. We explored whether patients with CSF NMDAR autoantibodies could be distinguished from patients with serum-only NMDAR autoantibodies. METHODS: The electronic databases MEDLINE, EMBASE, PubMed, and PsycINFO were searched. Articles reporting adult patients with isolated psychiatric features and positive for NMDAR autoantibodies with relevant investigations were included. Patient level meta-analysis compared patients positive for CSF NMDAR autoantibodies with patients positive for serum NMDAR autoantibodies, but negative for CSF NMDAR autoantibodies. Dichotomous data were analysed using crude odds ratios (OR), whilst continuous data were analysed using Mann–Whitney Test (U). The protocol was prospectively registered (CRD42018082210). RESULTS: Of 4413 publications, 42 were included, reporting 79 patients. Median age was 34 years (IQR 19 years); 56% (45/79) were female and 24% (16/68) had a tumour. In total, 41 patients were positive for CSF autoantibodies and 20 were positive for serum-only autoantibodies. Patients with CSF autoantibodies were significantly more likely to be female (p < 0.001) and have a rapid (< 3 month) onset of symptoms (p = 0.02) than patients with serum-only autoantibodies. They were also more likely to present with psychosis (p < 0.001), exhibit EEG (p = 0.006), MRI (p = 0.002), and CSF (p = 0.001) abnormalities, but less likely to present with insomnia (p = 0.04). CONCLUSIONS: Patients with an isolated psychiatric syndrome with CSF NMDAR autoantibodies can potentially be distinguished from those with serum-only NMDAR autoantibodies based on clinicodemographic and investigation findings. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00415-022-11224-6.